Design, synthesis, in vivo and in vitro studies of 1,2,3,4-tetrahydro-9H-carbazole derivatives, highly selective and potent butyrylcholinesterase inhibitors

Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism

“…38 also displayed neuroprotective effects against Aβ‐ and H 2 O 2 ‐induced cellular injuries on SH‐SY5Y cells. Considering the difficulties of synthesis, Ghobadian et al 202 simplified the well‐developed BChE inhibitory scaffold 2‐methyl‐9‐phenethyl‐2,3,4,9‐tetrahydro‐1 H ‐pyrido[3,4‐b]indole to 1,2,3,4‐tetrahydro‐9 H ‐carbazole and introduced structural modifications into the nitrogen‐containing heterocycles that lay in the end site of hydrocarbon chain. As expected, all of the synthesized molecules displayed inhibitory selectivity against eq BChE and the most potent compound 39 (Figure 13) was discovered to inhibit eq BChE with IC 50 value of 0.11 µM and SI of 893.…”

The selective butyrylcholinesterase inhibitor UW‐MD‐95 shows symptomatic and neuroprotective effects in a pharmacological mouse model of Alzheimer's disease

“…For instance, first, a series of carbazole derivatives showing nanomolar inhibitory potency on BChE and selectivity versus AChE were shown to attenuate scopolamine‐induced learning deficits in the water maze in rats. 29 , 49 Second, S06‐1011 and S06‐1031, two compounds containing a 3‐(benzimidazol‐2‐yl)‐1,2,5‐oxadiazole core, and showing a selective and sub‐micromolar inhibitory potency on BChE, attenuated scopolamine and Aβ 1‐42 ‐induced memory deficits in the Morris water maze in mice. 50 Third, sulfonamide derivatives of phenylglycine attenuated, after a 7‐day daily treatment before scopolamine, the memory deficits of rats in the Y‐maze and Barnes tests.…”

“… 52 BChE inhibitors have been shown to elicit direct anti‐oxidant activity in cellular models, particularly after cell exposure to H 2 O 2. 49 The drug may not indirectly exert its anti‐oxidant activity through specific protection of mitochondrial activity and homeostasis of the oxidative respiratory chain complex. 53 , 54 Second, UW‐MD‐95 attenuated Aβ 25‐35 ‐induced neuroinflammation.…”

“…Several BChE inhibitors have been previously reported to exert anti‐amnesic effects on scopolamine‐ and/or Aβ 1‐42 ‐induced impairments in rodents. For instance, first, a series of carbazole derivatives showing nanomolar inhibitory potency on BChE and selectivity versus AChE were shown to attenuate scopolamine‐induced learning deficits in the water maze in rats 29,49 . Second, S06‐1011 and S06‐1031, two compounds containing a 3‐(benzimidazol‐2‐yl)‐1,2,5‐oxadiazole core, and showing a selective and sub‐micromolar inhibitory potency on BChE, attenuated scopolamine and Aβ 1‐42 ‐induced memory deficits in the Morris water maze in mice 50 .…”

Oral administration of encapsulated catechin in chitosan‐alginate nanoparticles improves cognitive function and neurodegeneration in an aluminum chloride‐induced rat model of Alzheimer's disease

“…On the probe day, the hidden platform was removed, and the rats were placed in front of the target area, facing the wall. The Rats were allowed to swim freely for 60 s and the time spent in the target quadrant was recorded in order to assess their spatial memory (Ghobadian et al., 2018 ; Ghobadian et al., 2020 ; Ramin et al., 2011 ). All steps were performed under a blind procedure to ensure unbiased evaluation of animal assays.…”